The Center for the Neurobiology of Addiction Treatment (CNAT) is a renewal of a P50 Center at Wake Forest University Health Sciences that has been continuously funded by NIDA since 1991 and extensively re- designed at its last funding in 2009. The Specific Aims are: 1. to provide a novel mechanism of interaction among NIDA investigators at Wake Forest University to examine neurobiological mechanisms of cocaine pharmacotherapies, using tightly interacting projects to ensure an effective collaborative structure; 2. to provide a formal structure of collaborative interactions between our Center and our clinical partners at NIDA-funded clinical centers, thus providing a novel translational component to our research; 3. to provide a focus for the training of students and postdoctoral fellows in contemporary methods for investigating the neurobiological basis of drug abuse; 4. to serve as an information source to both the lay and scientific community on issues related to the neurobiological aspects of drug abuse. The scientific theme of the Center is focused on examining the neurobiological mechanisms of action of potential cocaine pharmacotherapeutic agents, with a focus on the use of drug combinations, using two treatment drugs that act through different pharmacological mechanisms to provide synergistic effects. The Center's novel strategy to identify potential drug combination pharmacotherapies is to utilize one drug that decreases cocaine reinforcement through the nucleus acumens dopaminergic pathway, with the other drug acting to reverse cocaine-induced deficits in cognition, i.e., cognitive remediators. The Center contains three cores and three major projects. The projects are highly interactive, with each project's activities dependent on results obtained from the other two projects. Project 1 will examine effects of combination drug treatment on various behavioral models in both rats and monkeys; Project 2 will explore how these combination drug treatment paradigms affect functional consequences in brain through neuro-imaging and voltammetry; and Project 3 will explore how these drug treatments affect gene expression, receptor function and signal transduction systems. The Center contains an Administrative Core and a Pilot Studies Core, while the Animal/Tissue Core will provide uniform sets of brain tissue samples from different rat models to the projects. These projects utilize several animal behavioral models and technologies uniquely developed by the Center investigators over the previous years of its funding history.